Abstract
Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10–20 nm) with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs) formed by recombinant full-length Hepatitis B virus core (HBc) protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL) led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.
Highlights
Vaccines offer the most cost-effective solution to prevent infectious and possibly non-infectious diseases, the rate of success in the vaccine development is currently declining [1]
The main goal of the present study was the evaluation of the adjuvant properties of the commercially available Silica nanopowder, with an original particle size of 10–20 nm, to provide a putative vaccine with high humoral and cell-mediated immune response in comparison to the traditional aluminium hydroxide (Alum), Complete Freund’s adjuvant (CFA) and incomplete Freund’s adjuvant (IFA) adjuvants
The Hepatitis B virus core (HBc) particles are distinguished by their extremely high intrinsic immunogenicity in hepatitis B patients [37], their capability to function as both T-cell-dependent and T-cell-independent antigens [38], and by their ability to induce strong B-cell and remarkably strong T-helper cell and cytotoxic T lymphocyte (CTL) responses [39,40,41]
Summary
Vaccines offer the most cost-effective solution to prevent infectious and possibly non-infectious diseases, the rate of success in the vaccine development is currently declining [1]. The reviving of vaccinology depends on the well-balanced improvement of two basic components of vaccines: the biological component and the adjuvant. While the current progress in the elaboration of numerous biological vaccine components is obvious [2, 3], the scope of safe and efficient adjuvants for human use is rather limited and needs an urgent expansion [2]. Two of them: a group of aluminium derivatives including aluminium phosphate, aluminium hydroxyphosphate, and aluminium hydroxide (Alum) and monophosphoryl lipid A (MPL) are licensed by the FDA for use in human vaccines today [5]. MPL, a TLR4 agonist, was licensed for human use in combination with Alum in a human papilloma virus vaccine [9]
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